Search

INTRODUCTION: In addition to formal training, informal training often occurs through a hidden curriculum. As the hidden curriculum shapes the knowledge and values held by learners, we must consider its role in implicit bias. One example is through the selection of images used in formal instruction. This study aimed to examine the representation of sex and race among images in two textbooks in emergency medicine (EM). METHODS: We performed a cross‐sectional study of the sex and race representation of figures in Rosen's Emergency Medicine: Concepts and Clinical Practice 9th Edition and Tintinalli's Emergency Medicine: A Comprehensive Study Guide 9th Edition. Two reviewers screened all images for inclusion, with disagreements resolved by a third reviewer. Images were excluded if they did not include visualized skin. Two reviewers independently reviewed each image and assessed the sex, race, and roles in the image. A third reviewer resolved any disagreements. RESULTS: A total of 959 images (Rosen's n = 377; Tintinalli's n = 582) met inclusion criteria. Race was estimated in 877 cases (91.3%). Of those, White individuals comprised 77.6% (95% confidence interval [CI] 75.0%–80.2%). Sex was estimated in 362 cases (37.7%). Of those images, males comprised 70.2% (95% CI 65.4%–74.9%), and females comprised 29.8% (95% CI 25.1%–34.6%). CONCLUSION: There is a male sex and White race predominance in visual representation among two EM textbooks. We propose a call to action for the mindful selection of images in formal education to represent diversity, equity, and inclusion and close the gap between the formal and hidden curriculum.

Many sensor systems, such as distributed wireless sensor arrays, require high-accuracy timing while maintaining low power consumption. Although the capabilities of chip-scale atomic clocks have advanced significantly, their cost continues to be prohibitive for many applications. GPS signals are commonly used to discipline local oscillators in order to inherit the long-term stability of GPS timing, however, commercially available GPS-disciplined oscillators typically use temperature-controlled oscillators and take an extended period of time to reach their stated accuracy, resulting in a large power consumption, usually over a watt. This has subsequently limited their adoption in low-power applications. Modern temperature-compensated crystal oscillators now have stabilities that enable the possibility of duty cycling a GPS receiver and intermittently correcting the oscillator for drift. Based on this principle, a design for a GPS-disciplined oscillator is presented that achieves an accuracy of 5 μμs rms in its operational environment, while consuming only 45 mW of average power. The circuit is implemented in a system called geoPebble, which uses a large grid of wireless sensors to perform glacial reflectometry.

Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Purpose There is an increasing interest in the use of donor-derived cfDNA (dd-cfDNA) in transplantation for non-invasive diagnosis of allograft injury. We hereby describe a non-commercial routine procedure for dd-cfDNA detection and quantification using digital droplet PCR and target-specific preamplification of a SNP-panel of 35 SNP-assays. The method is based on the difference in genotype between recipients and donors. After establishing our protocol, it has been used in a prospective study following recipients for 12 months after heart transplantation (HTx), and we here briefly describe our protocol. Methods A total of 728 samples from 67 HTx patients have been retrieved and analyzed. The recipients were genotyped preoperatively with respect to the SNP-panel. Upon transplantation, the donor genotype was interrogated with respect to the homozygous alleles found in the recipient. After HTx, blood samples were collected in cell free DNA collection tubes and delivered within the same day to the hospital laboratory. Plasma was separated by centrifugation at 2000g and 16000g, respectively. Isolated plasma was stored at -80C or used immediately for cfDNA extraction. Quality controls were performed by the 4200 Tape Station. The same primers were used for preamplification and downstream PCR. Non-template controls were included in all preamplification steps. The amount of dd-cfDNA was calculated as a fraction of the total cfDNA. Results The variation of extracted cfDNA yield was 10-130 ng/ml plasma. The 50-800 bp sized cfDNA constitutes 90% of the extracted samples, indicating a low background. An average of 2-5 informative SNPS assays for each transplant recipient were used for dd-cfDNA quantification with a detection rate down to 0.01% dd-cfDNA. Elevation of dd-cfDNA was seen not only in conjunction with cellular rejection but also during infection and in episodes of heart failure Conclusion Samples from HTx recipients demonstrated low levels of dd-cfDNA in consecutive samples during optimal treatment in non-eventful cases. Elevation of dd-cfDNA was seen not only during rejection but also in other conditions. This non-invasive method is relatively cheap, enables large sample yields by preamplification, has a fast turn-around time (48 hours) and is thus useful for clinical monitoring of HTx patients. However, it needs to be carefully related to clinical events.

The Navy's future and near-term high-energy sensors and energy weapons will consume a large portion of the resources of the intended ship platform. Many of these new systems will have extreme dynamic power profiles, including both periodic and aperiodic characteristics. These dynamics can cause sudden changes in power at the prime power system that can be stressing to platform systems, both to the generators and prime movers as well as other loads sharing the common distribution bus. This paper presents the use of a new adaptive power system (APS) to mitigate the negative impacts levied on the platforms resulting from large dynamic loads. A notional size of the hardware required to implement the APS design is presented along with simulation results verifying the concept.

Purpose Donor-derived cell-free DNA (dd-cfDNA) as a highly sensitive marker of rejection after heart transplantation (HTx) has gained emerging interest. Recent studies are based on sequencing techniques and use fractional abundance (dd-cfDNA as a fraction of total cfDNA) as their outcome. Here we present patient examples of the BIODRAFT-study (NCT03477383) based on PCR-techniques. Methods Blood samples are taken prospectively in parallel with endomyocardial biopsies (EMB) during the first year after HTx. dd-cfDNA is analyzed using targeted preamplification of 35 single nucleotide polymorphisms followed by digital droplet-PCR. Outcome is fractional abundance as well as total number of DNA copies, both from the donor and the recipient. Results 71 patients (57 adults, 14 children) are so far included and more than 500 blood samples analyzed. In otherwise stable patients, both fractional abundance and total DNA copies seem to follow biopsy patterns with respect to rejection. However, we could also identify different scenarios in which the distribution of cfDNA seems more complicated than hitherto described: Patients with primary graft failure, clinically silent CMV-infection or mild right heart failure show elevated levels of dd-cfDNA, thus complicating the interpretation of results. Some patients present with markedly elevated levels of their own cfDNA without obvious clinical reasons. Conclusion Besides the well-known concept of fractional abundance, our approach gives results that allow following absolute DNA copy numbers of both donor and recipient. This widens the horizon of cfDNA as a marker of graft injury after HTx, and gives an outlook to clinical scenarios with possible false positive (mimicking rejection) and, even worse, false negative results: high levels of recipient-cfDNA could mask ongoing rejection if only fractional abundance can be reported. The biology of cell-free DNA is complex and seems not yet fully understood.

This paper discusses the challenges of paralleling dual modules with special focus on the currently introduced dual modules like LinPak, nHPD2, XHP, LV/HV100, etc. Compared with IHM/IHV Modules 3 to 4 times as many modules have to be paralleled to achieve the same output power. Therefore the parallel connection will play a major role in designing high power converters, used e.g. in traction applications. This paper explains the reasons of current mismatch in parallel connection of IGBT modules and gives suggestions how to minimize current imbalance.

BackgroundStudies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.MethodsIn a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial.ResultsParticipants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events.ConclusionsAmong young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

We investigated the outcomes of injured patients who were undertriaged and compared them with those meeting full trauma team activation (TTA) criteria.Blunt trauma patients (July 2002-January 2008) meeting full TTA criteria and had a partial TTA were in the undertriage group (UTG). Data was collected on demographics, injury severity, OR delays, resource utilization, and outcomes. Excluded: penetrating trauma, transfers, burns, age18 years.Chi square, P.05, mean +/- SD.One thousand four hundred and twenty-four patients with 318 (22.3%) in the UTG and 1,106 in the correctly triaged group (CTG). The CTG was 70.4% male (vs 67.1%; P = .26), 41.5 +/- 19.8 years old (vs 45.8 +/- 20.5; P.01), and had an injury severity score (ISS) of 24.7 (vs 17.0; P.0001). The CTG was more likely to require ED intubation (34.9% vs 8.2%; P.0001), ICU admission (49.0% vs 37.1%; P.0001), longer ICU/hospital LOS, and more ventilator days (P.0001) with no differences in OR delays. The UTG had a lower mortality (6.0% vs 16.7%; P.0001) and were discharged home more often (65.3% vs 52.2%; P = .02).The UTG had a lower ISS and improved outcomes compared to the CTG with no differences in OR delays. Despite inherent challenges in TTA protocols, patients who were undertriaged at our institution appear to have satisfactory outcomes.

For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.A differential response occurred in 161 of 165 patients who were evaluated (P0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)

Background More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children. Objective The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control. Methods A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV 1 ≥ 80% predicted and methacholine FEV 1 PC 20 ≤ 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 μg twice daily (fluticasone monotherapy), fluticasone 100 μg/salmeterol 50 μg in the morning and salmeterol 50 μg in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements. Results Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV 1 /forced vital capacity ( P = .015), maximum bronchodilator response ( P = .009), exhaled nitric oxide ( P .001), and PC 20 ( P .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm). Conclusion Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups. Clinical implications Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV 1 ≥ 80% predicted, confirming current guideline recommendations.

Importance Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. Objective To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. Design, Setting, and Participants A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. Intervention Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. Main Outcomes and Measures The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. Results A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. Conclusions and Relevance Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. Trial Registration clinicaltrials.gov Identifier:NCT01272635

Background We sought to identify which adolescent patient characteristics might lead to subjective reported independence in accessing medical care when patients transition from pediatric to adult medicine. Methods Pediatric and adult rheumatologists were asked which pediatric patient characteristics they believed would improve transition to adult medical care. Based on these responses, a questionnaire was created and administered to 76 teenage/young adult patients in a pediatric rheumatology clinic. The first set of questions included demographic, disease features, and life skills questions. The second set of questions pertained to self-reported independence in managing medical care. Data was analyzed to see if there were any significant associations between an individual’s response to demographic, disease feature, or life skills questions and the independence outcome questions. Results In our study, older age correlated with self-reported independence in almost all questions asked regarding accessing medical care. Other patient characteristics that were associated with increased self-perceived autonomy included having a younger parent, having a family member with a similar disease, longer disease duration, having a comorbid non-rheumatic diagnosis, and having had a summer job. Conclusions The patient characteristics that we found associated with self-reported independence in obtaining medical care should be considered when determining which patients might be more likely to make a successful transition.

Physicians and others who provide expert testimony in court cases involving alleged child abuse may be instructed to state their conclusions within a 'reasonable medical certainty' (RMC). However, neither judges nor jurors knows what degree of probability constitutes RMC for a given expert, nor whether different experts use different standards to formulate their opinions. We sought to better understand how experts define RMC in the context of court cases. An email survey was sent to members of six list-serves, representing four specialties, whose members testify in child abuse cases. Respondents were asked to define how RMC corresponded to (1) the numerical probability that abuse occurred, (2) the ordinal probability, and (3) how their determinations relate to common legal standards ('preponderance of the evidence', 'clear and convincing', and 'beyond a reasonable doubt'). Participants were also asked how comfortable they were in defining RMC; whether their definition changed according to the charges or type of proceeding; and how they would apply RMC to several hypothetical cases. The 294 list-serve participants who responded included child abuse pediatricians (46%), forensic pathologists (21%), pediatric neurosurgeons (15%), pediatric ophthalmologists (12%), and others (6%). Though 95% of respondents had testified in court, only 45% had received training in the definition of RMC. Only 37% were comfortable defining RMC. Although many responses were highly clustered and paired comparisons showed that 95% of participants' responses were internally consistent, there was variability in respondents' definitions of RMC. There is some variability in how child abuse expert witnesses define and use the term RMC; we provide suggestions about how to more accurately and transparently define RMC to ensure justice in these cases.

Background Inhaled corticosteroids are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response. Objective Identify demographic, clinical, and atopic characteristics that may modify the inhaled corticosteroid treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma trial. Methods Children aged 6 to 18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment. Daily treatment consisted of 40 μg of beclomethasone twice daily. Rescue treatment consisted of 40 μg of beclomethasone accompanying each symptom-driven albuterol actuation. Combined treatment consisted of both. Outcomes included time to first exacerbation and proportion of asthma control days. Fourteen baseline characteristics were selected for interaction testing on the basis of their clinical relevance. Results Two hundred eighty-eight children were randomized. Seventy-five percent were white, and 55% were male. As measured by time to first exacerbation, 4 characteristics identified children who received greater benefit from treatment: non-Hispanic ethnicity, positive aeroallergen skin test result, serum immunoglobulin E level of 350 K/μL or more, and history of oral corticosteroid use in the year before enrollment. As measured by asthma control days, 4 characteristics identified children who received greater benefit from treatment: male sex, positive aeroallergen skin test result, serum immunoglobulin E level of 350 K/μL or more, and incomplete run-in asthma control. Conclusions Children with mild persistent asthma who have markers of atopic asthma or who have greater asthma burden may obtain greater benefit from beclomethasone therapy. Additional study is needed to confirm whether these markers can guide individualized therapy.

Background It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma. Methods We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 μg twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year. Results During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P = 0.006) and a lower rate of exacerbations (P

Background Few studies have characterized the atopic profile of toddler-aged children with recurrent wheezing at high risk of the development of persistent asthma. Objective We sought to determine the atopic profile of toddler-aged children with frequent wheeze at high risk for the development of persistent asthma who either had a parental history of asthma, a personal history of atopic dermatitis, or both. Methods Participants enrolled in the Prevention of Early Asthma in Kids study (n=285) on the basis of a modified Asthma Predictive Index were characterized on the basis of allergy and asthma questionnaire responses and allergy skin puncture test results. Results The majority of the children (60.7%, n=148) were sensitized to either food or aeroallergens. Male children were significantly more likely to be sensitized to aeroallergens ( P =.03) and to have a blood eosinophil level of 4% or greater ( P =.03) and a total serum IgE level of greater than 100 IU/mL ( P =.0004). Additionally, eosinophilia and total serum IgE level had the strongest correlation with aeroallergen sensitization. Conclusion The high prevalence of aeroallergen sensitization in this high-risk cohort suggests that aeroallergens might have an important role in the early development of asthma. As such, the Prevention of Early Asthma in Kids cohort appears to be an appropriate cohort in which to test whether early intervention with an inhaled corticosteroid can significantly attenuate, or perhaps even prevent, the allergic march from the initial stages of allergic sensitization to the subsequent development of asthma in toddlers with episodic wheezing.

A milk and serum ELISA containing lipoarabinomanan (LAM) antigen was evaluated in sheep and goats versus agar gel immunodiffusion (AGID) test and polymerase chain reaction (PCR) using milk and lymph nodes. Milk and serum samples were obtained from six, two, and four flocks with unknown, negative and positive status of infection, respectively. By comparison of serum ELISA activity and PCR results, the positive and negative predictive values were calculated. Receiver operation characteristic (ROC) analysis was used for calculating the specificity and sensitivity at different cut-offs.

Pediatric asthma remains an important public health concern as its prevalence and cost to the health care system is rising. In order to promote innovative research in asthma therapies, the National Heart, Lung and Blood Institute created the Childhood Asthma Research and Education Network in 1999. As its first study, the steering committee of the Childhood Asthma Research and Education Network designed a randomized clinical trial to determine if persistent asthma could be prevented in children at a high risk to develop the disease. This communication presents the design of its first clinical trial, the Prevention of Asthma in Kids (PEAK) trial and the organization of the Childhood Asthma Research and Education Network that developed and implemented this trial. Studies of the natural history of asthma have shown that, in persistent asthma, the initial asthma-like symptoms and loss of lung function occur predominately during the first years of life. Therefore, in the Prevention of Asthma in Kids study, children 2 and 3 years old with a positive asthma predictive index were randomized to twice daily treatment with fluticasone 88 microg or placebo via metered-dose inhaler and Aerochamber for 2 years. The double blind treatment period was followed by a 1-year observational period. Lung function was measured by spirometry and oscillometry technique at 4-month intervals throughout the study. Bronchodilator reversibility and exhaled nitric oxide (ENO) studies were performed at the end of the treatment and observation periods. The primary outcome measure was the number of asthma-free days. Other secondary outcomes included number of exacerbations, use of asthma medications and lung function. These measures were chosen to reflect the progression of the disease from intermittent wheezing to persistent asthma and measurement of the extent of airflow limitation and airway reactivity.

Recent blood pressure trends reflect progress in hypertension control, but prevalent drug therapy precludes direct estimation of the component due to primary prevention. In data gathered on persons aged 35-74 years in three successive US health examination surveys (1960-1980), systolic blood pressure levels assuming no drug therapy were imputed by reassigning blood pressure to the upper end of the distribution for respondents reporting use of antihypertensive medication. Blood pressure was partitioned into four ordinal categories based on weighted percentiles of the 1960-1962 distributions for 35- to 44-year-old males and females who reported no use of antihypertensive medication. Cumulative logit models (α = 0.01) were used to estimate age-and sex-specific trends for blacks and whites within two strata (

Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329.843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)-555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, p=0·03), combined (31%, 21-43, p=0·07), and rescue (35%, 24-47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5·6% (1·6-14) in the combined (p=0·012), 2·8% (0-10) in the daily (p=0·009), and 8·5% (2-15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided.National Heart, Lung and Blood Institute.

Objectives: Attending professional continuing education (CE) is an important component of librarianship. This research study identified librarians' preferences in delivery modalities of instruction for professional CE. The study also identified influential factors associated with attending CE classes. Methods: Five instruction-delivery modalities and six influential factors were identified for inclusion in an online survey. The survey completed by members of the American Library Association (ALA), Special Libraries Association (SLA), and Medical Library Association (MLA) provided the data for analysis of librarian preferences and influential factors. Results: The majority of respondents were MLA members, followed by ALA and SLA members. Librarians from all three library associations preferred the face-to-face instructional modality. The most influential factor associated with the decision to attend a professional CE class was cost. Conclusions: All five instruction-delivery modalities present useful structures for imparting professional CE. As librarians' experience with different modalities increases and as technology improves, preferences in instruction delivery may shift. But at present, face-to-face remains the most preferred modality. Based on the results of this study, cost was the most influential factor associated with attending a CE class. This may change as additional influential factors are identified and analyzed in future studies.

Background In children with mild-to-moderate persistent asthma, identification of phenotypic predictors to guide selection of a controller regimen is essential. Objective We sought to identify phenotypic characteristics having predictive value for the difference in treatment responses between twice-daily fluticasone and once-daily montelukast. Methods Data from the Pediatric Asthma Controller Trial were assessed with multivariate analysis. Outcomes included the change in asthma control days (ACDs), FEV 1 , peak expiratory flow, and time to first asthma exacerbation measured over a 1-year treatment period. Results The mean age was 9.6 ± 2.1 years, 60% were male, 50% had a parental history of asthma, and 78% had positive aeroallergen skin prick test responses. The mean percent predicted prebronchodilator FEV 1 was 97.8% ± 12.9%, the median PC 20 value was 0.93 mg/mL, and the median exhaled nitric oxide (eNO) level was 25.2 ppb. A history of parental asthma best predicted the expected treatment benefit with fluticasone compared with montelukast in terms of gain in ACDs (adjusted P = .02) and time to first exacerbation (adjusted P = .05). Increased baseline eNO levels predicted the differential treatment response for fluticasone regarding the gain in ACDs (adjusted P = .01). Prior inhaled corticosteroid (ICS) use (adjusted P = .01) and low PC 20 values (adjusted P = .03) each predicted the expected treatment benefit with fluticasone over montelukast regarding time to first exacerbation. No phenotypic characteristics predicted treatment benefits for montelukast over fluticasone for either outcome. Conclusions Physicians treating children with a parental history of asthma, increased eNO levels, low PC 20 values, or a history of ICS use can expect the best long-term outcomes with ICS therapy compared with treatment with leukotriene receptor antagonists.

The capacity for dental treatment under general anaesthesia is limited. Clearly, the demand for treatment exceeds the supply. A written questionnaire completed by all 403 patients who were treated in 2003 in a centre for special dentistry under general anaesthesia, or their parents or carers, revealed that the median time between referral and the first consultation was 8 weeks. The median time between the first consultation and treatment was also 8 weeks. The waiting period for children was longer than that for adults, with that for 4- and 5-year-olds the longest of all. During the waiting period, 43% of the patients developed complications, such as oral pain and problems with eating and sleeping. Children developed complications more often than adults. With every week of waiting, the likelihood of children developing complications increased by 6.7%.

Well-designed data management processes are essential in ensuring the quality of data collected in multicenter clinical trials. This paper describes the data management processes and systems that were developed by the data coordinating center of the Asthma Clinical Research Network. A combination of manual and electronic processes has been designed to process clinical trial data from the point of collection to statistical analysis. A distributed database management system consisting of modular applications for separate data processing activities was developed to enter, track, verify, validate, and edit collected data. In addition, processes for monitoring and reporting data quality are discussed.

A relation exists between colloid osmotic pressure (pi) and serum total protein concentration; equations describing this relation have been used to determine a calculated value for pi. However, the relation between total protein concentration and pi is altered by the method used to measure protein and by changes in the ratio of concentrations of albumin (A) to globulin (G). We developed nomograms for estimating pi from A and G concentrations, using samples obtained from clinically normal animals and compared the accuracy of these nomograms with that of previously described equations relating pi to total protein concentration. For comparison, serum samples from canine (n = 106), equine (n = 79), feline (n = 24), and bovine (n = 27) patients admitted to the University of Georgia Veterinary Medical Teaching Hospital were used. Results indicated that nomograms based on protein concentration estimated by a refractometer generally were the least reliable. Although predictive nomograms, using total protein concentration determined by the biuret method, provided better results for serum samples, there was considerable variation between measured and calculated values for pi in all species studied. Calculated values for pi derived from A and G concentrations were most closely related to measured values for pi in dogs, horses, and cats. However, calculated values for pi differed from measured values by as much as 5 mm of Hg for some samples by each of the methods of estimation.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits. However, determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment. Objective To determine if demographic and atopic features predict response to ICS in preschool children at high risk for asthma. Methods Two years of treatment with an ICS, fluticasone propionate (88 μg twice daily), was compared with matching placebo in a double-masked, randomized, multicenter study of 285 children 2 and 3 years old at high risk for asthma development. Baseline demographic and atopic features were related to clinical outcomes in a post hoc subgroup analysis. Results Multivariate analysis demonstrated significantly greater improvement with fluticasone than placebo in terms of episode-free days among boys, white subjects, participants with an emergency department (ED) visit or hospitalization within the past year, and those who experienced more symptomatic days at baseline. Children with aeroallergen sensitization experienced greater benefits in terms of oral corticosteroid use, urgent care and ED visits, and use of supplemental controller medications. Conclusions More favorable responses to ICS than placebo in high-risk preschool children over a 2-year period were more likely in those with a ED visit or hospitalization for asthma within the past year, children with aeroallergen sensitization, boys, and white subjects.

Background Determination of the benefits and limitations of specific physiologic tests has not been well studied in long-term clinical pediatric trials. Objective We sought to determine the utility of impulse oscillometry in a long-term comparison of 3 controller regimens in children with persistent asthma. Methods Children 6 to 14 years of age with mild-to-moderate persistent asthma were characterized with oscillometry and spirometry before entry into a clinical trial and then serially during 48 weeks of therapy with either an inhaled corticosteroid, a combination inhaled corticosteroid with a long-acting β-agonist, or a leukotriene receptor antagonist. Results The FEV 1 /forced vital capacity ratio, as well as the forced expiratory flow from 25% to 75% of forced vital capacity in terms of spirometric parameters and the reactance area (XA) from impulse oscillometry, appeared to complement information provided by FEV 1 when comparing the tests and factors that appeared to predict a response to treatment. XA was unique in that it, as distinct from spirometric variables, reflected ongoing improvement during the latter part of the trial. In general, improvements in XA during the latter part of the study occurred independently of indices of atopy and the level of airway responsiveness. Conclusion Assessment of respiratory mechanics over time with oscillometry might offer additional insights into the response of asthmatic patients to therapy. In particular, the pattern of improvement seen in XA over the course of therapy suggests this test might detect alterations in airway mechanics not reflected by spirometry. The possibility that changes in XA reflect ongoing improvement in small airway function deserves additional study.

A technique is described for isolating nuceoli from Acanthamoeba castellanii. Nuclei isolated by a modification of the technique of F. J. Chlapowski and R. N. Band (1971) are sonicated in a surcrose-Tris-MgSO4-KC1-Triton X-100 buffer and centrifuged on a linear sucrose gradient extending from 1.3 M to 1.5 M with a 2.6 M cushion, at 41000 rpm for 90 min. The only apparent contaminants in the nucleolar preparation are outer cyst walls. A procedure is described for the isolation of chemically pure outer cyst walls, and a comparison of the proteins with the nucleolar preparation reveals that outer cyst walls represent negligible contaminants. The ultrastructure of these isolated nucleoli examined with transmission electron microscopy is found to be identical with that of nucleoli from whole cells, fixed in an identical manner. The 50 nucleolar proteins separated by SDS gel electrophoresis have been examined throughout the growth cycle of Acanthamoeba and into the strat of induced encystment, at which time 10 protein bands disappear, 11 bands are observed to decrease, and 8 are seen to increase in concentration. Phenol-soluble proteins are extracted from the nucleolus which correspond to 29 of the 50 nucleolar proteins, with 17 of these proteins corresponding to nucleolar proteins that change at the onset of encystment. Thes nucleolar proteins are also compared with those of rat liver nucleoli by gel electrophoresis, resulting in the observation that extremely few protein homologies exist between the two. Numerous quantitative and qualitative changes in the gel pattern of phenol-soluble nuclear proteins during early and late log phase growth and the onset of stationary phase were also observed.

Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).

AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. Fil: McMurray, John J. V.. University of Glasgow; Reino Unido Fil: Anand, Inder S.. University of Minnesota; Estados Unidos Fil: Diaz, Rafael. Estudios Clínicos Latinoamérica; Argentina Fil: Maggioni, Aldo P.. Associazione Nazionale Medici Cardiologi Ospedalieri; Italia Fil: O'Connor, Christopher. University of Duke; Estados Unidos Fil: Pfeffer, Marc A.. Brigham and Women’s Hospita; Estados Unidos Fil: Solomon, Scott D.. Brigham and Women’s Hospital; Estados Unidos Fil: Tendera, Micha. Medical University of Silesia; Polonia Fil: van Veldhuisen, Dirk J.. University of Groningen; Países Bajos Fil: Moetaz, Albizem. Amgen Inc.; Estados Unidos Fil: Cheng, Sunfa. Amgen Inc.; Estados Unidos Fil: Scarlata, Debra. Amgen Inc.; Estados Unidos Fil: Swedberg, Karl. University of Gothenburg; Suecia Fil: Young, James B.. Cleveland Clinic. Endocrinology and Metabolism Institute; Estados Unidos Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: RED-HF Committees Investigators. No especifíca